EP0453898A2 - Use of TNF-specific antibodies as a drug for treatment of ischemias and of their consequences - Google Patents
Use of TNF-specific antibodies as a drug for treatment of ischemias and of their consequences Download PDFInfo
- Publication number
- EP0453898A2 EP0453898A2 EP91105829A EP91105829A EP0453898A2 EP 0453898 A2 EP0453898 A2 EP 0453898A2 EP 91105829 A EP91105829 A EP 91105829A EP 91105829 A EP91105829 A EP 91105829A EP 0453898 A2 EP0453898 A2 EP 0453898A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- tnf
- treatment
- consequences
- ischemias
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/241—Tumor Necrosis Factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- the present invention relates to the use of monoclonal anti-TNF antibodies for the treatment of ischemia and the associated side effects, such as tissue damage, in particular their use in medicaments for reducing arrhythmias, for heart attacks, reducing myocardial infarction, and for increasing the survival rate after myocardial infarction.
- tumor necrosis factor encompasses two cytotoxic factors (TNF- ⁇ and TNF- ⁇ ), which are largely formed by activated lymphocytes and monocytes.
- TNF released from bacterial infections is known to cause tumor decline in cancer.
- anti-TNF antibodies are published which treat diseases such as sept. Shock, graft rejection, allergies, autoimmune diseases, shock lung, blood clotting disorders or inflammatory bone diseases that are associated with an increase in TNF in the blood can be used for inactivation.
- EP 230 574 describes antibodies against TNF which can be used for the treatment of LAV / HTV III virus infections.
- Ischemia can be used in the treatment of ischemia and its consequences. Ischemias often result in massive tissue damage, especially after reperfusion, which often leads to death. Tissue damage can be limited and the mortality rate reduced by administration of antibodies against TNF. Ischemia is understood here to mean conditions in which the blood supply to the organs or parts of organs is interrupted or Typical ischemic clinical pictures are acute myocardial infarction, brain infarction, tourniquet syndrome, but also poly traumas. This also includes interruptions in the blood supply in the case of transplants from, for example, the heart, kidney, liver, lung or in the case of replantations or in the case of poisoning of the lungs. In all of these indications, antibodies against TNF can reduce or prevent secondary damage to organs and tissues.
- Monoclonal antibodies against TNF are particularly suitable for the treatment of acute myocardial infarction and the associated arrhythmias and tissue damage, in particular for use in medicaments for reducing arrhythmias, reducing infarct sizes and for increasing the survival rate after myocardial infarction.
- the present invention includes pharmaceutical preparations which, in addition to non-toxic, inert pharmaceuticals suitable carriers which contain the compounds according to the invention, and processes for the preparation of these preparations.
- the pharmaceutical preparations listed above can also contain further active pharmaceutical ingredients.
- the pharmaceutical preparations listed above are prepared in a conventional manner by known methods, e.g. by mixing the active substance or substances with the carrier substance or substances.
- the active ingredient (s) in total amounts of about 0.5 to about 500, preferably 1 to 100 mg / kg of body weight per 24 hours, if appropriate in the form of several individual doses, in order to achieve the desired results .
- a single dose contains the active ingredient (s) preferably in amounts of about 1 to about 80, in particular 1 to 30 mg / kg body weight.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Die vorliegende Erfindung betrifft die Verwendung von monoklonalen anti-TNF-Antikörpern zur Behandlung von Ischämien und den damit verbundenen Begleiterscheinungen, wie Gewebsschädigungen, insbesondere ihre Verwendung in Arzneimitteln zur Arrhythmienreduktion, bei Herzinfarkten, Infarktgrößenreduktion und zur Erhöhung der Überlebensrate nach Myokard-Infarkt.The present invention relates to the use of monoclonal anti-TNF antibodies for the treatment of ischemia and the associated side effects, such as tissue damage, in particular their use in medicaments for reducing arrhythmias, for heart attacks, reducing myocardial infarction, and for increasing the survival rate after myocardial infarction.
Es ist bekannt, daß der Begriff Tumor Necrosis Faktor (TNF) zwei zytotoxische Faktoren (TNF-α und TNF-β) umfaßt, die größtenteils von aktivierten Lymphozyten und Monozyten gebildet werden. Außerdem ist bekannt, daß bei bakteriellen Infektionen freigesetztes TNF einen Rückgang des Tumors bei Krebserkrankungen bewirkt.It is known that the term tumor necrosis factor (TNF) encompasses two cytotoxic factors (TNF-α and TNF-β), which are largely formed by activated lymphocytes and monocytes. In addition, TNF released from bacterial infections is known to cause tumor decline in cancer.
Es wurde in Untersuchungen festgestellt, daß einige Erkrankungen, wie Parasiten-Infektionen, alkoholbedingte Lebererkrankungen, Hepatitis, Pl.-Falciparum-Malaria, rheumatoide Arthritis, Nierentransplantationen, Multiple Sklerose und Verletzungen mit einer starken Erhöhung des TNF-Spiegels verbunden sind, die oft lebensbedrohend werden kann [vgl. Z.A. Bharat, B. Aggarwal in "Drugs of the Future", 12 (1987), S. 891 ff.; American Journal of Medicine 87/2 (139-143), 1989; Transplantation 47 (4), 606-608, 1989].Studies have shown that some diseases, such as parasite infections, alcohol-related liver diseases, hepatitis, Pl.-Falciparum malaria, rheumatoid arthritis, kidney transplants, multiple sclerosis and injuries are associated with a sharp increase in TNF levels, which can often be life-threatening [cf. ZA Bharat, B. Aggarwal in "Drugs of the Future", 12 (1987), p. 891 ff .; American Journal of Medicine 87/2 (139-143), 1989; Transplantation 47 (4), 606-608, 1989].
In der Publikation EP 260 010 werden beispielsweise Anti-TNF-Antikörper publiziert, die bei Krankheiten wie sept. Schock, Transplantatabstoßung, Allergien, Autoimmunkrankheiten, Schocklunge, Blutgerinnungsstörungen oder entzündlichen Knochenerkrankungen, die mit einer Erhöhung von TNF im Blut verbunden sind, zur Inaktivierung eingesetzt werden können.In the publication EP 260 010, for example, anti-TNF antibodies are published which treat diseases such as sept. Shock, graft rejection, allergies, autoimmune diseases, shock lung, blood clotting disorders or inflammatory bone diseases that are associated with an increase in TNF in the blood can be used for inactivation.
Ebenso werden in der EP 230 574 Antikörper gegen TNF beschrieben, die zur Behandlung von LAV/HTV III-Virus-Infektionen eingesetzt werden können.Likewise, EP 230 574 describes antibodies against TNF which can be used for the treatment of LAV / HTV III virus infections.
Überraschenderweise wurde nun gefunden, daß Antikörper gegen TNF bei der Behandlung von Ischämien und deren Folgen eingesetzt werden können. So kommt es bei Ischämien insbesondere nach Reperfusion oft zu massiven Gewebeschädigungen, die vielfach zum Tode führen. Durch Gabe von Antikörpern gegen TNF läßt sich der Gewebeschaden begrenzen und die Letalitätsquote senken. Unter Ischämie werden hier Zustände verstanden, bei die Blutzufuhr zur Organen bzw. Organteilen unterbrochen bzw. reduziert ist.Typsich ischämische Krankheitsbilder sind der akute Herzinfarkt, der Hirninfarkt, Tourniquet-Syndrom, aber auch Polytraumen. Ebenso dazu gehören Unterbrechungen der Blutzufuhr bei Transplantationen von z.B. Herz, Niere, Leber, Lunge oder bei Replantationen oder bei Vergiftung der Lunge. Bei all diesen Indikationen können Antikörper gegen TNF die sekundären Schäden in Organen und Geweben reduzieren bzw. verhüten.Surprisingly, it has now been found that antibodies against TNF can be used in the treatment of ischemia and its consequences. Ischemias often result in massive tissue damage, especially after reperfusion, which often leads to death. Tissue damage can be limited and the mortality rate reduced by administration of antibodies against TNF. Ischemia is understood here to mean conditions in which the blood supply to the organs or parts of organs is interrupted or Typical ischemic clinical pictures are acute myocardial infarction, brain infarction, tourniquet syndrome, but also poly traumas. This also includes interruptions in the blood supply in the case of transplants from, for example, the heart, kidney, liver, lung or in the case of replantations or in the case of poisoning of the lungs. In all of these indications, antibodies against TNF can reduce or prevent secondary damage to organs and tissues.
Besonders geeignet sind monoklonale Antikörper gegen TNF zur Behandlung von akutem Herzinfarkt und den damit verbundenen Arrhythmien und Gewebsschädigungen, insbesondere zur Verwendung in Arzneimitteln zur Arrhythmienreduktion, Infarktgrößenreduktion und zur Erhöhung der Überlebensrate nach Myokard-Infarkt.Monoclonal antibodies against TNF are particularly suitable for the treatment of acute myocardial infarction and the associated arrhythmias and tissue damage, in particular for use in medicaments for reducing arrhythmias, reducing infarct sizes and for increasing the survival rate after myocardial infarction.
Die monoklonalen Antikörper und die Verfahren zu ihrer Herstellung sind bekannt [vgl. US 4 603 106, EP 260 610; EP 218 868 und Köhler und Milstein, Nature 256, 495-497 (1975); Current Topics in Microbiology and Immunology Vol. 81: Lymphocyte Hybridomas, Springer Verlag 1978; Monoclonal Antibodies, Kennet et al., Plenum Press 1980, S. 363-419].The monoclonal antibodies and the processes for their preparation are known [cf. US 4,603,106, EP 260,610; EP 218 868 and Köhler and Milstein, Nature 256 , 495-497 (1975); Current Topics in Microbiology and Immunology Vol. 81: Lymphocyte Hybridomas, Springer Verlag 1978; Monoclonal Antibodies, Kennet et al., Plenum Press 1980, pp. 363-419].
Die pharmakologische Wirkung wurde am narkotisierten Schwein und Rhesusaffen gefunden, bei denen experimentell die Durchblutung reduziert wurde.The pharmacological effects were found in anesthetized pigs and rhesus monkeys, in which the blood flow was experimentally reduced.
Zur vorliegenden Erfindung gehören pharmazeutische Zubereitungen, die neben nicht-toxischen, inerten pharmazeutisch geeigneten Trägerstoffen die erfindungsgemäßen Verbindungen enthalten, sowie Verfahren zur Herstellung dieser Zubereitungen.The present invention includes pharmaceutical preparations which, in addition to non-toxic, inert pharmaceuticals suitable carriers which contain the compounds according to the invention, and processes for the preparation of these preparations.
Die oben aufgeführten pharmazeutischen Zubereitungen können außer den erfindungsgemäßen Verbindungen auch weitere pharmazeutische Wirkstoffe enthalten.In addition to the compounds according to the invention, the pharmaceutical preparations listed above can also contain further active pharmaceutical ingredients.
Die Herstellung der oben aufgeführten pharmazeutischen Zubereitungen erfolgt in üblicher Weise nach bekannten Methoden, z.B. durch Mischen des oder der Wirkstoffe mit dem oder den Trägerstoffen.The pharmaceutical preparations listed above are prepared in a conventional manner by known methods, e.g. by mixing the active substance or substances with the carrier substance or substances.
Im allgemeinen hat es sich als vorteilhaft erwiesen, den oder die erfindungsgemäßen Wirkstoffe in Gesamtmengen von etwa 0,5 bis etwa 500, vorzugsweise 1 bis 100 mg/kg Körpergewicht je 24 Stunden, gegebenenfalls in Form mehrerer Einzelgaben, zur Erzielung der gewünschten Ergebnisse zu verabreichen. Eine Einzelgabe enthält den oder die Wirkstoffe vorzugsweise in Mengen von etwa 1 bis etwa 80, insbesondere 1 bis 30 mg/kg Körpergewicht. Es kann jedoch erforderlich sein, von den genannten Dosierungen abzuweichen, und zwar in Abhängigkeit von der Art und dem Körpergewicht des zu behandelnden Objekts, der Art und der Schwere der Erkrankung, der Art der Zubereitung und der Applikation des Arzneimittels sowie dem Zeitraum bzw. Intervall, innerhalb welchem die Verabreichung erfolgt.In general, it has proven to be advantageous to administer the active ingredient (s) according to the invention in total amounts of about 0.5 to about 500, preferably 1 to 100 mg / kg of body weight per 24 hours, if appropriate in the form of several individual doses, in order to achieve the desired results . A single dose contains the active ingredient (s) preferably in amounts of about 1 to about 80, in particular 1 to 30 mg / kg body weight. However, it may be necessary to deviate from the doses mentioned, depending on the type and body weight of the object to be treated, the type and severity of the disease, the type of preparation and administration of the drug, and the period or interval within which the administration takes place.
Claims (3)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4013114 | 1990-04-25 | ||
DE4013114 | 1990-04-25 | ||
DE4037604A DE4037604A1 (en) | 1990-04-25 | 1990-11-27 | Use of anti-TNF antibodies to treat ischaemia and its sequelae - esp. to increase survival rate after myocardial infarct and transplants |
DE4037604 | 1990-11-27 |
Publications (3)
Publication Number | Publication Date |
---|---|
EP0453898A2 true EP0453898A2 (en) | 1991-10-30 |
EP0453898A3 EP0453898A3 (en) | 1991-12-18 |
EP0453898B1 EP0453898B1 (en) | 1995-05-31 |
Family
ID=25892502
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP91105829A Expired - Lifetime EP0453898B1 (en) | 1990-04-25 | 1991-04-12 | Use of TNF-specific antibodies as a drug for treatment of ischemias and of their consequences |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP0453898B1 (en) |
JP (1) | JPH04364133A (en) |
AT (1) | ATE123226T1 (en) |
DE (2) | DE4037604A1 (en) |
DK (1) | DK0453898T3 (en) |
ES (1) | ES2073059T3 (en) |
IL (1) | IL97909A (en) |
Cited By (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994020139A1 (en) * | 1993-03-10 | 1994-09-15 | Knoll Aktiengesellschaft | Use of anti-tnf antibodies as medicament for the therapy of heart insufficiency (weakness of the heart muscle) |
US5436154A (en) * | 1990-12-28 | 1995-07-25 | Farmitalia Carlo Erba S.R.L. | Monoclonal antibodies against human Tumor Necrosis Factor α |
WO1997030088A2 (en) * | 1996-02-16 | 1997-08-21 | The Kennedy Institute Of Rheumatology | Methods of treating vascular disease with tnf antagonists |
WO2004016286A2 (en) | 2002-08-16 | 2004-02-26 | Abbott Biotechnology Ltd. | Pharmaceutical anti-tnf-alpha antibody formulation |
US6790444B2 (en) | 1991-03-18 | 2004-09-14 | New York University Medical Center | Anti-TNF antibodies and peptides of human necrosis factor |
WO2005110452A2 (en) | 2004-04-09 | 2005-11-24 | Abbott Biotechnology Ltd. | MULTIPLE-VARIABLE DOSE REGIMEN FOR TREATING TNFα-RELATED DISORDERS |
US7101674B2 (en) | 1991-03-18 | 2006-09-05 | New York University | Anti-idiotypic anti-TNF antibodies and related immunoassay methods |
US7128908B2 (en) | 1991-03-18 | 2006-10-31 | Centocor, Inc. | Methods for treating systemic lupus erythematosus using anti-TNF antibodies and fragments thereof |
EP2196218A2 (en) | 2002-04-26 | 2010-06-16 | Abbott Biotechnology Ltd | Use of anti-TNFalpha antibodies and another drug |
US7815909B2 (en) | 2000-08-07 | 2010-10-19 | Centocor, Inc. | Anti-TNF antibodies, compositions, methods and uses |
EP2295071A1 (en) | 2002-10-24 | 2011-03-16 | Abbott Biotechnology Ltd | Low dose methods for treating disorders in which TNF-alpha activity is detrimental |
EP2305712A1 (en) | 1996-02-09 | 2011-04-06 | Abbott Biotechnology Ltd | Human antibodies that bind human TNFalpha |
EP2324851A1 (en) | 2001-06-08 | 2011-05-25 | Abbott Biotechnology Ltd | Methods of administering anti-TNFalpha antibodies |
EP2738178A1 (en) | 2006-04-05 | 2014-06-04 | AbbVie Biotechnology Ltd | Antibody purification |
US8986693B1 (en) | 2004-04-09 | 2015-03-24 | Abbvie Biotechnology Ltd. | Use of TNFα inhibitor for treatment of psoriasis |
WO2015073884A2 (en) | 2013-11-15 | 2015-05-21 | Abbvie, Inc. | Glycoengineered binding protein compositions |
US9365645B1 (en) | 2011-04-27 | 2016-06-14 | Abbvie, Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
WO2016160976A2 (en) | 2015-03-30 | 2016-10-06 | Abbvie Inc. | Monovalent tnf binding proteins |
EP3078676A1 (en) | 2015-04-10 | 2016-10-12 | Ares Trading S.A. | Induction dosing regimen for the treatment of tnf alpha mediated disorders |
US9499616B2 (en) | 2013-10-18 | 2016-11-22 | Abbvie Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
US9505833B2 (en) | 2012-04-20 | 2016-11-29 | Abbvie Inc. | Human antibodies that bind human TNF-alpha and methods of preparing the same |
US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9522953B2 (en) | 2013-10-18 | 2016-12-20 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9598667B2 (en) | 2013-10-04 | 2017-03-21 | Abbvie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
US9605064B2 (en) | 2006-04-10 | 2017-03-28 | Abbvie Biotechnology Ltd | Methods and compositions for treatment of skin disorders |
US9683033B2 (en) | 2012-04-20 | 2017-06-20 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9688752B2 (en) | 2013-10-18 | 2017-06-27 | Abbvie Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
US9708399B2 (en) | 2013-03-14 | 2017-07-18 | Abbvie, Inc. | Protein purification using displacement chromatography |
US9708400B2 (en) | 2012-04-20 | 2017-07-18 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
WO2018124948A1 (en) | 2016-12-30 | 2018-07-05 | Закрытое Акционерное Общество "Биокад" | AQUEOUS PHARMACEUTICAL COMPOSITION OF A RECOMBINANT MONOCLONAL ANTIBODY TO FNOα |
US10465003B2 (en) | 2016-02-05 | 2019-11-05 | Janssen Biotech, Inc. | Anti-TNF antibodies, compositions, methods and use for the treatment or prevention of type 1 diabetes |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1989008460A1 (en) * | 1988-03-11 | 1989-09-21 | Celltech Limited | Antibodies for use in antilymphocyte antibody therapy |
EP0351789A2 (en) * | 1988-07-18 | 1990-01-24 | Chiron Corporation | Improved monoclonal antibodies reactive with cachectin |
-
1990
- 1990-11-27 DE DE4037604A patent/DE4037604A1/en not_active Withdrawn
-
1991
- 1991-04-12 EP EP91105829A patent/EP0453898B1/en not_active Expired - Lifetime
- 1991-04-12 ES ES91105829T patent/ES2073059T3/en not_active Expired - Lifetime
- 1991-04-12 DE DE59105609T patent/DE59105609D1/en not_active Expired - Fee Related
- 1991-04-12 DK DK91105829.5T patent/DK0453898T3/en active
- 1991-04-12 AT AT91105829T patent/ATE123226T1/en not_active IP Right Cessation
- 1991-04-19 JP JP3115535A patent/JPH04364133A/en active Pending
- 1991-04-22 IL IL97909A patent/IL97909A/en not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1989008460A1 (en) * | 1988-03-11 | 1989-09-21 | Celltech Limited | Antibodies for use in antilymphocyte antibody therapy |
EP0351789A2 (en) * | 1988-07-18 | 1990-01-24 | Chiron Corporation | Improved monoclonal antibodies reactive with cachectin |
Non-Patent Citations (5)
Title |
---|
°SCIENCE, Band 249, Nr. 4964, 06 Juli 1990, Washington, DC (US); A. LEFER et al., Seiten 61-64/ * |
°TRANSPLANTATION, Band 49, Nr. 2, Februar 1990, Baltimore, MD (US); L. COLLETTI et al., Seiten 268-272/ * |
Journal of Clinical Investigation, Bd. 85, Nr. 6, Juni 1990, New York, USA, Seiten 1936-1943; L. COLLETTI et al.: "Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat", Zusammenfassung. * |
Science, Bd. 249, Nr. 4964, 6. Juli 1990, Washington DC, USA, Seiten 61-64; A. LEFER et al.: "Mediation of cardioprotection by transforming growth factor-beta", Zusammenfassung. * |
Transplantation, Bd. 49, Nr. 2, Februar 1990, Baltimore, USA, Seiten 268-272; L. COLLETTI et al.: "The production of tumor necrosis factor alpha and the development of a pulmonary capillary injury following hepatic ischemia/reperfusion", Zusammenfassung. * |
Cited By (100)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5436154A (en) * | 1990-12-28 | 1995-07-25 | Farmitalia Carlo Erba S.R.L. | Monoclonal antibodies against human Tumor Necrosis Factor α |
US7335358B2 (en) | 1991-03-18 | 2008-02-26 | Centocor, Inc. | Methods of treating psoriasis with anti-TNF antibodies |
US7276239B2 (en) | 1991-03-18 | 2007-10-02 | Centocor, Inc. | Recombinant A2-specific TNFα-specific antibodies |
US7744885B2 (en) | 1991-03-18 | 2010-06-29 | Centocor, Inc. | Methods of treating vascular inflammatory pathology using anti-TNF antibodies and fragments thereof |
US7374761B2 (en) | 1991-03-18 | 2008-05-20 | Centocor, Inc. | Recombinant A2-specific TNFα-specific antibodies |
US6790444B2 (en) | 1991-03-18 | 2004-09-14 | New York University Medical Center | Anti-TNF antibodies and peptides of human necrosis factor |
US7425330B2 (en) | 1991-03-18 | 2008-09-16 | Centocor, Inc. | Methods of inhibiting TNFα activity in the blood of a patient |
US6835823B2 (en) | 1991-03-18 | 2004-12-28 | New York University | Anti-TNF antibodies and peptides of human tumor necrosis factor |
US7135178B2 (en) | 1991-03-18 | 2006-11-14 | Centocor, Inc. | Methods of treating disseminated intravascular coagulation using anti-TNF antibodies |
US7070775B2 (en) | 1991-03-18 | 2006-07-04 | New York University | Recombinant A2-specific TNFα specific antibodies |
US7101674B2 (en) | 1991-03-18 | 2006-09-05 | New York University | Anti-idiotypic anti-TNF antibodies and related immunoassay methods |
US7128908B2 (en) | 1991-03-18 | 2006-10-31 | Centocor, Inc. | Methods for treating systemic lupus erythematosus using anti-TNF antibodies and fragments thereof |
US7128907B2 (en) | 1991-03-18 | 2006-10-31 | Centocor, Inc. | Methods of treating crohn's disease with anti-TNF antibodies |
US7135179B2 (en) | 1991-03-18 | 2006-11-14 | Centocor, Inc. | Methods for treating sarcoidosis using anti-TNF antibodies and fragments thereof |
US7404955B2 (en) | 1991-03-18 | 2008-07-29 | Centocor, Inc. | Methods of inhibiting or neutralizing TNFα in patients with tissue injury |
US7138118B2 (en) | 1991-03-18 | 2006-11-21 | Centocor, Inc. | Methods of treating rheumatoid arthritis with anti-TNF antibodies |
US7160542B2 (en) | 1991-03-18 | 2007-01-09 | New York University | Method of treating psoriasis using human anti-TNF antibodies and fragments |
US7160543B2 (en) | 1991-03-18 | 2007-01-09 | New York University | Methods of inhibiting TNF-α in patients with Crohn's disease |
US7160995B2 (en) | 1991-03-18 | 2007-01-09 | New York University | DNA encoding anti-TNF antibodies and peptides |
US7166284B2 (en) | 1991-03-18 | 2007-01-23 | New York University | Methods of treating joint inflammation with anti-TNF antibodies |
US7169386B1 (en) | 1991-03-18 | 2007-01-30 | New York University | Methods of treating inflammation associated with viral infection with anti-TNF antibodies |
US7169388B2 (en) | 1991-03-18 | 2007-01-30 | New York University | Methods of inhibiting TNFα in patients with cancer |
US7179893B2 (en) | 1991-03-18 | 2007-02-20 | New York University | Recombinant anti-TNF-α antibodies |
US7179466B2 (en) | 1991-03-18 | 2007-02-20 | New York University | Methods of treating rheumatoid arthritis by multiple administration of anti-TNF antibodies |
US7192584B2 (en) | 1991-03-18 | 2007-03-20 | Centocor, Inc. | Methods of treating psoriasis with anti-TNF antibodies |
US7204985B2 (en) | 1991-03-18 | 2007-04-17 | Centocor, Inc. | Methods of treating disseminated intravascular coagulation by multiple administration of anti-TNF antibodies |
US7214376B2 (en) | 1991-03-18 | 2007-05-08 | New York University | Methods of inhibiting TNFα in patients with neoplastic disease |
US7223396B2 (en) | 1991-03-18 | 2007-05-29 | Centocor, Inc. | Methods of treatment of fistulas in Crohn's disease with anti-TNF antibodies |
US7227003B2 (en) | 1991-03-18 | 2007-06-05 | New York University | Anti-TNF antibody fragments |
US7226593B2 (en) | 1991-03-18 | 2007-06-05 | Centocor, Inc. | Methods of treating cachexia with chimeric anti-TNF antibodies |
US7252823B2 (en) | 1991-03-18 | 2007-08-07 | Centocor, Inc. | Recombinant A2-specific TNFα-specific antibodies |
US7416729B2 (en) | 1991-03-18 | 2008-08-26 | Centocor, Inc. | Methods of treating rheumatoid arthritis with anti-TNF antibodies |
WO1994020139A1 (en) * | 1993-03-10 | 1994-09-15 | Knoll Aktiengesellschaft | Use of anti-tnf antibodies as medicament for the therapy of heart insufficiency (weakness of the heart muscle) |
EP2305712A1 (en) | 1996-02-09 | 2011-04-06 | Abbott Biotechnology Ltd | Human antibodies that bind human TNFalpha |
EP2930187A1 (en) | 1996-02-09 | 2015-10-14 | AbbVie Biotechnology Ltd | Human antibodies that bind human tnfalpha |
EP2933267A1 (en) | 1996-02-09 | 2015-10-21 | AbbVie Biotechnology Ltd | Human antibodies that bind human tnfalpha |
EP2357200A1 (en) | 1996-02-09 | 2011-08-17 | Abbott Biotechnology Ltd | Human antibodies that bind human TNFalpha |
EP2930186A1 (en) | 1996-02-09 | 2015-10-14 | AbbVie Biotechnology Ltd | Human antibodies that bind human tnfalpha |
EP2930185A1 (en) | 1996-02-09 | 2015-10-14 | AbbVie Biotechnology Ltd | Human antibodies that bind human tnfalpha |
EP2397494A1 (en) | 1996-02-09 | 2011-12-21 | Abbott Biotechnology Ltd | Human antibodies that bind human TNFalpha |
EP2305713A1 (en) | 1996-02-09 | 2011-04-06 | Abbott Biotechnology Ltd | Human antibodies that bind human TNFalpha |
EP1460087A1 (en) * | 1996-02-16 | 2004-09-22 | The Kennedy Institute Of Rheumatology | Methods of treating vascular disease with TNF antagonists |
WO1997030088A3 (en) * | 1996-02-16 | 1997-10-09 | Kennedy Inst Of Rheumatology | Methods of treating vascular disease with tnf antagonists |
WO1997030088A2 (en) * | 1996-02-16 | 1997-08-21 | The Kennedy Institute Of Rheumatology | Methods of treating vascular disease with tnf antagonists |
US20090263388A1 (en) * | 1996-02-16 | 2009-10-22 | The Kennedy Institute Of Rheumatology | Methods of preventing or treating cardiovascular, cerebrovascular and thrombotic disorders with tumor necrosis factor antagonists |
US7608262B2 (en) | 1996-02-16 | 2009-10-27 | The Kennedy Institute Of Rheumatology | Methods of preventing or treating thrombosis with tumor necrosis factor antagonists |
US7820169B2 (en) | 2000-08-07 | 2010-10-26 | Centocor, Inc. | Anti-TNF antibodies, compositions, methods and uses |
US7815909B2 (en) | 2000-08-07 | 2010-10-19 | Centocor, Inc. | Anti-TNF antibodies, compositions, methods and uses |
EP2324851A1 (en) | 2001-06-08 | 2011-05-25 | Abbott Biotechnology Ltd | Methods of administering anti-TNFalpha antibodies |
EP2940044A1 (en) | 2001-06-08 | 2015-11-04 | AbbVie Biotechnology Ltd | Methods of administering anti-tnfalpha antibodies |
EP2359855A2 (en) | 2001-06-08 | 2011-08-24 | Abbott Biotechnology Ltd | Methods of administering anti-TNFalpha antibodies |
EP3190124A1 (en) | 2001-06-08 | 2017-07-12 | AbbVie Biotechnology Ltd | Adalimumab for use in therapy of rheumatoid arthritis |
EP2364731A2 (en) | 2001-06-08 | 2011-09-14 | Abbott Biotechnology Ltd | Methods of administering anti-TNFalpha antibodies |
EP2347766A1 (en) | 2002-04-26 | 2011-07-27 | Abbott Biotechnology Ltd | Use of TNFalpha antibodies and another drug |
EP2196218A2 (en) | 2002-04-26 | 2010-06-16 | Abbott Biotechnology Ltd | Use of anti-TNFalpha antibodies and another drug |
US9090689B1 (en) | 2002-07-19 | 2015-07-28 | Abbvie Biotechnology Ltd. | Use of TNFα inhibitor for treatment of psoriasis |
US9950066B2 (en) | 2002-08-16 | 2018-04-24 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
EP2363145A1 (en) | 2002-08-16 | 2011-09-07 | Abbott Biotechnology Ltd | Pharmaceutical anti-TNF-alpha antibody formulation |
EP2363144A1 (en) | 2002-08-16 | 2011-09-07 | Abbott Biotechnology Ltd | Pharmaceutical anti-TNF-alpha antibody formulation |
EP2361637A1 (en) | 2002-08-16 | 2011-08-31 | Abbott Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9732152B2 (en) | 2002-08-16 | 2017-08-15 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
EP2359856A1 (en) | 2002-08-16 | 2011-08-24 | Abbott Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9738714B2 (en) | 2002-08-16 | 2017-08-22 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
WO2004016286A2 (en) | 2002-08-16 | 2004-02-26 | Abbott Biotechnology Ltd. | Pharmaceutical anti-tnf-alpha antibody formulation |
US9750808B2 (en) | 2002-08-16 | 2017-09-05 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-alpha associated disorders |
EP2295071A1 (en) | 2002-10-24 | 2011-03-16 | Abbott Biotechnology Ltd | Low dose methods for treating disorders in which TNF-alpha activity is detrimental |
EP2332565A1 (en) | 2002-10-24 | 2011-06-15 | Abbott Biotechnology Ltd. | Low dose methods for treating disorders in which TNFalpha activity is detrimental |
EP2335732A2 (en) | 2004-04-09 | 2011-06-22 | Abbott Biotechnology Ltd | Multiple-variable dose regimen for treating TNF-alpha-related disorders |
US9512216B2 (en) | 2004-04-09 | 2016-12-06 | Abbvie Biotechnology Ltd. | Use of TNFα inhibitor |
US8986693B1 (en) | 2004-04-09 | 2015-03-24 | Abbvie Biotechnology Ltd. | Use of TNFα inhibitor for treatment of psoriasis |
US8889136B2 (en) | 2004-04-09 | 2014-11-18 | Abbvie Biotechnology Ltd. | Multiple-variable dose regimen for treating TNFα-related disorders |
WO2005110452A2 (en) | 2004-04-09 | 2005-11-24 | Abbott Biotechnology Ltd. | MULTIPLE-VARIABLE DOSE REGIMEN FOR TREATING TNFα-RELATED DISORDERS |
EP2335731A2 (en) | 2004-04-09 | 2011-06-22 | Abbott Biotechnology Ltd | Multiple-variable dose regimen for treating TNF-alpha-related disorders |
EP2338516A2 (en) | 2004-04-09 | 2011-06-29 | Abbott Biotechnology Ltd | Multiple-variable dose regimen for treating TNF-alpha-related disorders |
EP2738178A1 (en) | 2006-04-05 | 2014-06-04 | AbbVie Biotechnology Ltd | Antibody purification |
EP3088410A2 (en) | 2006-04-05 | 2016-11-02 | AbbVie Biotechnology Ltd | Antibody purification |
EP2738179A1 (en) | 2006-04-05 | 2014-06-04 | AbbVie Biotechnology Ltd | Antibody purification |
US9605064B2 (en) | 2006-04-10 | 2017-03-28 | Abbvie Biotechnology Ltd | Methods and compositions for treatment of skin disorders |
US9365645B1 (en) | 2011-04-27 | 2016-06-14 | Abbvie, Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9505834B2 (en) | 2011-04-27 | 2016-11-29 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9957318B2 (en) | 2012-04-20 | 2018-05-01 | Abbvie Inc. | Protein purification methods to reduce acidic species |
US9505833B2 (en) | 2012-04-20 | 2016-11-29 | Abbvie Inc. | Human antibodies that bind human TNF-alpha and methods of preparing the same |
US9708400B2 (en) | 2012-04-20 | 2017-07-18 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
US9683033B2 (en) | 2012-04-20 | 2017-06-20 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9708399B2 (en) | 2013-03-14 | 2017-07-18 | Abbvie, Inc. | Protein purification using displacement chromatography |
US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
US9598667B2 (en) | 2013-10-04 | 2017-03-21 | Abbvie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
US9522953B2 (en) | 2013-10-18 | 2016-12-20 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9688752B2 (en) | 2013-10-18 | 2017-06-27 | Abbvie Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
US9499616B2 (en) | 2013-10-18 | 2016-11-22 | Abbvie Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
US9550826B2 (en) | 2013-11-15 | 2017-01-24 | Abbvie Inc. | Glycoengineered binding protein compositions |
WO2015073884A2 (en) | 2013-11-15 | 2015-05-21 | Abbvie, Inc. | Glycoengineered binding protein compositions |
WO2016160976A2 (en) | 2015-03-30 | 2016-10-06 | Abbvie Inc. | Monovalent tnf binding proteins |
EP3078676A1 (en) | 2015-04-10 | 2016-10-12 | Ares Trading S.A. | Induction dosing regimen for the treatment of tnf alpha mediated disorders |
WO2016162537A1 (en) | 2015-04-10 | 2016-10-13 | Ares Trading S.A | Induction dosing regimen |
EP3078675A1 (en) | 2015-04-10 | 2016-10-12 | Ares Trading S.A. | Induction dosing regimen for the treatment of tnf alpha mediated disorders |
US10465003B2 (en) | 2016-02-05 | 2019-11-05 | Janssen Biotech, Inc. | Anti-TNF antibodies, compositions, methods and use for the treatment or prevention of type 1 diabetes |
US11124565B2 (en) | 2016-02-05 | 2021-09-21 | Janssen Biotech, Inc. | Method for treating pre-type 1 diabetes in a human subject |
WO2018124948A1 (en) | 2016-12-30 | 2018-07-05 | Закрытое Акционерное Общество "Биокад" | AQUEOUS PHARMACEUTICAL COMPOSITION OF A RECOMBINANT MONOCLONAL ANTIBODY TO FNOα |
Also Published As
Publication number | Publication date |
---|---|
ATE123226T1 (en) | 1995-06-15 |
DE59105609D1 (en) | 1995-07-06 |
IL97909A (en) | 1997-09-30 |
JPH04364133A (en) | 1992-12-16 |
DE4037604A1 (en) | 1991-10-31 |
EP0453898A3 (en) | 1991-12-18 |
ES2073059T3 (en) | 1995-08-01 |
IL97909A0 (en) | 1992-06-21 |
DK0453898T3 (en) | 1995-10-09 |
EP0453898B1 (en) | 1995-05-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0453898B1 (en) | Use of TNF-specific antibodies as a drug for treatment of ischemias and of their consequences | |
DE60223670T2 (en) | Fatty acids as factors for survival and activation of neutrophils. | |
EP0857065B1 (en) | Use of 2-amino-4-(4-fluorobenzylamino)-1-ethoxy-carbonylaminobenzene for prophylaxis and treatment of sequelae of acute and chronic reduced circulation in the brain and neurodegenerative disorders | |
DE69929810T2 (en) | USE OF TETRACYCLINE DERIVATIVES TO INCREASE INTERLEUKIN-10 PRODUCTION | |
DE3305755A1 (en) | N-PHENYL-BENZAMIDE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE IN THE FIGHT AGAINST DISEASES OF THE IMMUNE SYSTEM | |
WO1994020139A1 (en) | Use of anti-tnf antibodies as medicament for the therapy of heart insufficiency (weakness of the heart muscle) | |
EP0236951A2 (en) | Use of diphenyl hydantoin and its derivatives in the preparation of a pharmaceutical agent for the treatment of immune diseases | |
EP0461499A2 (en) | Use of efomycins A, E and G as antiinflammatory agents | |
DE69835591T2 (en) | INDUCTORS FOR IMMUNOL TOLERANCE | |
DE3737274A1 (en) | Use of pure H2A and/or H2B histone as active substance for the production of pharmaceutical compositions | |
EP0271023A2 (en) | Use of dihydrophenylamino-acid derivatives and medicines containing them for immunomodulation and cytostasis | |
EP1227808B1 (en) | Use of treosulfan for patient conditioning before bone marrow or blood stem cell transplantation | |
DE2528460A1 (en) | 1-Carbamoyl 2-cyano aziridine as immunostimulant - for therapy of bacterial and viral infections | |
AT408719B (en) | AGENT FOR TREATING HEPATITIS C | |
DE3134709A1 (en) | ANTINEOPLASTIC TITANIUM COMPOUND AND MEDICINAL PRODUCTS CONTAINING THEM | |
DE60012183T2 (en) | USE OF A MACROLIDE COMPOUND FOR PRODUCING A MEDICINE FOR TREATING BRAIN DAMAGE DUE TO ISCHEMIA OR BLEEDING | |
EP1528922B1 (en) | Use of treosulfan and derivatives thereof for treating multiple sclerosis | |
DE4312916C2 (en) | Medicines used to treat immune reactions | |
DE3603242C2 (en) | ||
EP0669826A1 (en) | Drug containing (-)-metriphonate | |
DE19711795C2 (en) | Use of cyclosporin for the treatment of myocardial infarctions and their consequences | |
DE69826795T2 (en) | Staphylococcus aureus therapy | |
DE69829992T2 (en) | METHOD FOR MOBILIZING HEMATOPOIETIC STEM CELLS | |
CH647151A5 (en) | AGENT AGAINST TUMORS. | |
DE4345200A1 (en) | Pharmaceutical composition for the treatment of immune reactions |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE |
|
PUAL | Search report despatched |
Free format text: ORIGINAL CODE: 0009013 |
|
AK | Designated contracting states |
Kind code of ref document: A3 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE |
|
17P | Request for examination filed |
Effective date: 19920115 |
|
17Q | First examination report despatched |
Effective date: 19940415 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE |
|
REF | Corresponds to: |
Ref document number: 123226 Country of ref document: AT Date of ref document: 19950615 Kind code of ref document: T |
|
REF | Corresponds to: |
Ref document number: 59105609 Country of ref document: DE Date of ref document: 19950706 |
|
GBT | Gb: translation of ep patent filed (gb section 77(6)(a)/1977) |
Effective date: 19950612 |
|
ET | Fr: translation filed | ||
ITF | It: translation for a ep patent filed |
Owner name: ING. C. GREGORJ S.P.A. |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2073059 Country of ref document: ES Kind code of ref document: T3 |
|
REG | Reference to a national code |
Ref country code: GR Ref legal event code: FG4A Free format text: 3016725 |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: T3 |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
26N | No opposition filed | ||
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 19980316 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GR Payment date: 19980320 Year of fee payment: 8 Ref country code: FR Payment date: 19980320 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: SE Payment date: 19980324 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 19980403 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 19980415 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: AT Payment date: 19980417 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DK Payment date: 19980424 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: ES Payment date: 19980428 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: BE Payment date: 19980429 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NL Payment date: 19980430 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: LU Payment date: 19980504 Year of fee payment: 8 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990412 Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990412 Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990412 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990413 Ref country code: ES Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990413 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990430 Ref country code: GR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990430 Ref country code: DK Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990430 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990430 Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990430 |
|
BERE | Be: lapsed |
Owner name: BAYER A.G. Effective date: 19990430 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: NL Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19991101 |
|
GBPC | Gb: european patent ceased through non-payment of renewal fee |
Effective date: 19990412 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19991231 |
|
NLV4 | Nl: lapsed or anulled due to non-payment of the annual fee |
Effective date: 19991101 |
|
EUG | Se: european patent has lapsed |
Ref document number: 91105829.5 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: ST |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20000201 |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: EBP |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FD2A Effective date: 20010503 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES;WARNING: LAPSES OF ITALIAN PATENTS WITH EFFECTIVE DATE BEFORE 2007 MAY HAVE OCCURRED AT ANY TIME BEFORE 2007. THE CORRECT EFFECTIVE DATE MAY BE DIFFERENT FROM THE ONE RECORDED. Effective date: 20050412 |